During the last year the interest in the potential of telomerase inhibitors grew substantially in part due to very recent reports providing experimental proof of the concept that telomerase inhibitors can cause death of tumor cells by preventing the renewal of their telomeres resulting in shortening below a threshold telomeric DNA size. These data also provided opportunity to analyze the complex dynamics of cell division and telomere size distributions. We have been developing a dynamic model of these processes for many years but for the first time we were able to compare its predictions with accurately measured experimental data of cell dynamics in well defined conditions. Our previous data were obtained for in vivo situation which is much more complex and therefore much more difficult to analyze. However, the combination of the two sets of data (in vitro and in vivo) provided unique opportunity to quantitatively analyze the telomere and tumor dynamics and how telomerase inhibitors affect it. Perhaps the most interesting result is that treatment with telomerase inhibitors in vivo may result in an immediate effect in contrast to the predominant current thinking that a relatively long delay will exist after treatment initiation before telomerase inhibitors affect tumor growth. This result may have implications for the further development of telomerase inhibitors. Even more interesting from theoretical point of view is the finding that with a relatively simple set of differential equations we can quantitatively fit simultaneously several independent sets of experimental data. An important result is that the data are best fitted if we assume the existence of two subpopulations of cells - rapidly dividing and very slowly dividing cells. We also analyzed cell dynamics in patients with HIV infections. A major result was that T lymphocytes contain two subpopulations of cells - rapidly and slowly dividing. The number of rapidly dividing cells, but not that of slowly dividing cells, correlated with the amount of HIV in the blood plasma suggesting that the proliferation of the short lived cells is caused by immune activation due to viral antigens. This finding has potential implications for understanding HIV pathogenesis and specifically the mechanisms of CD4 cell number decline with the progression of the disease. An analysis of acute SIV and SHIV infections in macaques suggested that very early stages of these infections could be important for the subsequent clinical outcome. It appears that the competition between virus replication and immune responses during the first weeks of infection may be important for the immunopathogenesis. These results could be important for vaccine development and early treatments. Finally, we analyzed several cohorts of patients treated with potent combination of antiretroviral drugs and confirmed our previous finding for a single cohort of children that by measuring HIV dynamics during the first week of treatment one can predict with 80-90% certainty the treatment efficacy. This result is very important because it allows early change in therapy if inefficient thus avoiding potential development of drug resistant mutants and drug toxicity. Z01 BC 10042-04